Peptidergic neuromodulation of microcircuits that control chemosensation-induced behaviors

控制化学感觉诱导行为的微电路肽能神经调节

• 批准号: 10132286
• 负责人: KENTA ASAHINA
• 金额: $ 41.23万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132286
• 关键词: Acetylcholine; Address; Affect; Afferent Neurons; Aggressive behavior; Agonistic Behavior; Alleles; Ally; Anatomy; Animals; Anxiety; Arousal; Behavior; Behavioral; Behavioral Mechanisms; Biological Models; Brain; Cells; Chemicals; Choline; Cues; Data; Defect; Disease; Dissection; Drosophila genus; Drosophila melanogaster; Event; FMRFamide; Food; Functional disorder; Genetic; Goals; Human; Hunger; Knock-in; Knowledge; Lead; Measures; Mediating; Mental disorders; Modeling; Molecular; Morphology; Nervous system structure; Neuraxis; Neuromodulator; Neurons; Neuropeptide Receptor; Neuropeptides; Neurotransmitters; Pathology; Peptide Synthesis; Peptides; Perception; Pheromone; Physiological; Physiological Processes; Physiology; Plant Roots; Play; Population; Process; Reagent; Research; Resolution; Role; Sensory; Signal Transduction; Site; Smell Perception; Stimulus; Study models; Synapses; System; Tachykinin; Tachykinin Receptor; Taste Perception; Testing; Work; base; behavioral response; combinatorial; cost effective; experimental study; fast-acting neurotransmitter; improved; in vivo calcium imaging; knowledge base; male; neural circuit; neuronal circuitry; neuropeptide F; neuroregulation; neurotransmitter release; optogenetics; receptor; relating to nervous system; reproductive; response; sensory stimulus; success; synergism; tool; vinegar fly

PROJECT SUMMARY Neuropeptides play important roles in modulating neural circuits that process olfactory and gustatory infor- mation. This modulation generally functions to align an animal's internal state (e.g., levels of arousal, or food status) with behavioral responses to sensory stimuli (e.g., pheromones or food-associated odorants). Although the neuropeptidergic modulation of specific sensory neurons has been described, the molecular and cellular mechanisms by which neuropeptides affect central chemosensory circuits are unknown. The long-term goal is to characterize the neuropeptidergic modulation of chemosensory circuits by deconstructing this physiological process into clearly defined, behaviorally relevant molecular and neuronal events. Importantly, altered chemosensation in humans is often associated with certain types of mental disorders, and characterizing at a molecular level the neuropeptidergic modulation of chemosensation is a fundamental first step toward under- standing and improving treatments for these disorders. The Drosophila model system offers an excellent plat- form for these studies, because neuropeptidergic systems can be precisely manipulated and the effects on well-characterized circuits mediating chemosensation-induced behaviors, such as male aggressive behavior, can be measured. Initial experiments will focus on the neuropeptide tachykinin, with the central hypothesis that neuropeptides act locally to affect a specific population of neurons to modulate chemosensory information rele- vant to male agonistic behavior. The three specific aims, each based on preliminary success, are to: 1) charac- terize the neuropeptidergic circuit that modulates pheromone-induced male agonistic behavior, 2) characterize synergies between neuropeptides and co-released neurotransmitters, and 3) elucidate the cellular basis of in- teractions among three neuropeptide (tachykinin, neuropeptide F and FMRFamide) that each modulate male agonistic behavior (a chemosensation-guided behavior). In Aim 1, neurons expressing the tachykinin receptor (Takr86C) will be morphologically characterized, and those receiving synaptic input from aggression-promoting tachykininergic neurons will be identified via photo-activatable GFP-assisted neuronal tracing and in vivo cal- cium imaging. In Aim 2, interactions between tachykinin and the co-expressed neurotransmitter acetylcholine will be characterized. Peptide or transmitter release will be independently blocked in relevant cells, and effects on downstream neuronal activity and behavior will be analyzed. In Aim 3, anatomical and physiological rela- tionships between neurons expressing tachykinin, neuropeptide F, or FMRFamide will be established, leading to a better understanding of how these three neuropeptides synergistically affect a pheromone-processing neu- ral circuit. Together, the research proposed here will uncover the genetic and cellular mechanisms by which neuropeptides physiologically affect chemosensory circuits to modulate behavior. Such knowledge will provide a fundamental understanding of how smell and taste perception is centrally controlled, and how dysfunction of this process may lead to non-adaptive responses to environmental cues.

项目摘要 神经肽在调节嗅觉和味觉信息的神经回路中起重要作用 mation。该调节通常起作用以使动物的内部状态保持一致（例如，唤醒或食物的水平 状态）具有对感觉刺激的行为反应（例如，信息素或食物相关的气味剂）。虽然 已经描述了特定感觉神经元的神经肽调节，分子和细胞 神经肽会影响中央化学感应电路的机制尚不清楚。长期目标是 通过解构该生理学来表征化学感应电路的神经肽调节 处理明确定义的，行为相关的分子和神经元事件。重要的是，改变了 人类的化学一密度通常与某些类型的精神障碍有关，并在 分子水平的化学一致化神经肽调节是迈向不足的基本第一步 站立并改善这些疾病的治疗方法。果蝇模型系统提供了出色的平台 这些研究的形式，因为可以精确操纵神经肽系统，并且对 介导化学敏度诱导的行为（例如男性侵略行为）的特征良好的电路， 可以测量。最初的实验将集中于神经肽速肽，并以中心假设为 神经肽在本地起作用，以影响特定的神经元群体，以调节化学水敏信息 对男性激动人心的行为。每个基于初步成功的三个特定目标是：1）特征 - 修复调节信息素诱导的男性激动性行为的神经肽电路，2）表征 神经肽和共同发行的神经递质之间的协同作用，3）阐明 每种神经肽（速肽，神经肽F和FMRFAMIDE）之间的畸形，每个神经肽都调节雄性 激动性行为（一种化学敏化引导的行为）。在AIM 1中，表达速素受体的神经元 （takr86c）将在形态学上表征，而那些从侵略性促进的人会接受突触输入 速毒素能神经元将通过可拍摄的GFP辅助神经元跟踪和体内鉴定 CIUM成像。在AIM 2中，旋转基因蛋白与共表达的神经递质乙酰胆碱之间的相互作用 将被描述。肽或发射机释放将在相关细胞中独立阻塞，并影响 将分析下游神经元活动和行为。在AIM 3中，解剖学和生理关系 将建立表达速蛋白，神经肽F或FMRFAMIDE的神经元之间的影响，领先 为了更好地理解这三种神经肽如何协同影响信息素化的neu- 拉尔电路。总之，这里提出的研究将发现遗传和细胞机制 神经肽在生理上影响化学感应回路以调节行为。这样的知识将提供 对气味和味觉感知的中心控制方式的基本了解，以及如何功能障碍 此过程可能会导致对环境线索的非自适应反应。